Our work continues to focus on two approaches to hematopoietic differentiation. First, we demonstrated previously that expression of a c-myc or c-myb transgene reversibly blocks terminal differentiation of a mouse erythroleukemia cell line. We are now using this system to test mutated c-myb transgenes so that we can begin to understand how c-myb affects proliferation and differentiation. Our long term goal is to understand the mechanisms that are responsible for the apparent inability of most hematopoietic tumors to differentiate. Second, we have developed a novel method for subtractive cloning by incorporating polymerase chain reaction (PCR) technology into the preparation and analysis of subtractive CDNA libraries. We have used this novel methodology to identify genes which are expressed in most murine plasmacytomas but rarely in B lymphomas. Thus far, we have identified two classes of genes having this property: 1) two genes are expressed in most plasmacytoma and pre-B lymphoma cell lines; and 2) five genes are expressed in most plasmacytoma cell lines but not in pre-B lymphoma lines. The predicted coding sequences and expression patterns in normal tissues and other cell lines suggest that some of these genes are involved in the phenotype of the normal plasma cell, whereas other genes may be involved in the tumorigenic process since they are not expressed in normal plasma cells. Our long term goal is to identify the genes which determine the phenotypes of plasmacytomas and terminally differentiated plasma cells.